Epithelial Downgrowth After Type 1 Boston Keratoprosthesis Manifesting As Tractional Retinal Detachment and Epiretinal Membrane

Table. All Consented Patients With Type 1 ROP in at Least 1 Eye

Consented Patients With ROP, No. Patients Developing Birth Weight, g Race (N = 2320) Type 1 ROP, No. (%) Ͻ750 Non–African American 623 186 (29.9) African American 315 36 (11.4) 750-999 Non–African American 726 140 (19.3) African American 233 18 (7.7) Ն1000 Non–African American 331 25 (7.6) African American 92 1 (1.1) Total Non–African American 1680 351 (20.9) African American 640 55 (8.6)

Abbreviation: ROP, retinopathy of prematurity.

focus on infants particularly likely to develop ROP. How- 1. Good WV, Hardy RJ, Dobson V, et al; Early Treatment for Retinopathy of Pre- ␤ maturity Cooperative Group. The incidence and course of retinopathy of pre- ever, any study of the effects of -blocker therapy must ad- maturity: findings from the Early Treatment for Retinopathy of Prematurity dress the fragility of the patients to be tested and possible Study. Pediatrics. 2005;116(1):15-23. systemic and ocular adverse effects. Nevertheless, if topi- 2. Early Treatment for Retinopathy of Prematurity Cooperative Group. Revised ␤ indications for the treatment of retinopathy of prematurity: results of the Early cal -blockers prove to be effective in preventing some cases Treatment for Retinopathy of Prematurity randomized trial. Arch Ophthalmol. of ROP, this opens the door for a more individualized ap- 2003;121(12):1684-1694. ␤ 3. Saunders RA, Donahue ML, Christmann LM, et al; Cryotherapy for Retinopa- proach to prevention of the disease, eg, using -adrener- thy of Prematurity Cooperative Group. Racial variation in retinopathy of gic receptor polymorphisms to guide ROP management. prematurity. Arch Ophthalmol. 1997;115(5):604-608. 4. Liggett SB, Cresci S, Kelly RJ, et al. A GRK5 polymorphism that inhibits beta- adrenergic receptor signaling is protective in heart failure. Nat Med. 2008; William V. Good, MD 14(5):510-517. 5. Praveen V, Vidavalur R, Rosenkrantz TS, Hussain N. Infantile hemangiomas Robert J. Hardy, PhD and retinopathy of prematurity: possible association. Pediatrics. 2009;123 David K. Wallace, MD, MPH (3):e484-e489. Don Bremer, MD 6. Le´aute´-Labrèze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taı¨eb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008; David L. Rogers, MD 358(24):2649-2651. R. Michael Siatkowski, MD Inge De Becker, MD, FRCSC C. Gail Summers, MD Rae Fellows, MEd Epithelial Downgrowth After Type 1 Boston Betty Tung, MS Keratoprosthesis Manifesting as Earl A. Palmer, MD Tractional Retinal Detachment and Epiretinal Membrane Author Affiliations: Smith-Kettlewell Eye Research In- stitute, San Francisco, California (Dr Good); School of ype 1 Boston keratoprosthesis (KPro) is a vi- Public Health, University of Texas Health Science Cen- able treatment option for corneal disease at high ter at Houston (Dr Hardy and Ms Tung); Duke Eye Cen- T risk for graft failure with traditional penetrat- ter, Durham, North Carolina (Dr Wallace). The Ohio State ing keratoplasty. Postoperative complications of Boston University College of Medicine (Drs Bremer and Rog- KPro include retroprosthetic membrane, glaucoma, ster- ers) and Department of Ophthalmology, Nationwide Chil- ile vitritis, infectious endophthalmitis, corneal melt, ex- dren’s Hospital (Drs Bremer and Rogers and Ms Fel- trusion, and retinal detachment.1 To our knowledge, we lows), Columbus; Department of Ophthalmology, Dean report the first case of epithelial downgrowth (ED) of the McGee Eye Institute, University of Oklahoma, Okla- posterior segment after Boston KPro placement. homa City (Dr Siatkowski); Departments of Ophthal- mology (Drs De Becker and Summers) and Pediatrics (Dr Report of a Case. A 52-year-old man with a history of Summers), University of Minnesota, Minneapolis; and penetrating ocular injury to his right eye had open globe Casey Eye Institure, Oregon Health and Science Univer- repair and cataract extraction in 1974, placement of a sec- sity, Portland (Dr Palmer). ondary anterior chamber intraocular lens in 1992, 2 failed Correspondence: Dr Good, Smith-Kettlewell Eye Re- penetrating keratoplasty procedures in 2004 and 2008, search Institute, 2318 Fillmore St, San Francisco, CA Baerveldt glaucoma tube implantation in 2005, astig- 94115 ([email protected]). matic keratotomy in 2007, and, most recently, intraocu- Financial Disclosure: None reported. lar lens removal and type 1 Boston KPro placement in Funding/Support: This work was supported by grants 2010. Histologic examination of the failed corneal graft 5U10 EY12471 and 5U10 EY12472 from the National In- excised at the time of KPro placement did not demon- stitutes of Health. strate ED. One week after KPro placement, visual acuity Trial Registration: clinicaltrials.gov Identifier: was 20/40 OD. Two months after KPro placement, he had NCT00027222 pain and photophobia in the right eye.

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Figure 1. Clinical presentation of epithelial downgrowth. A, Slitlamp examination reveals an intraprosthetic membrane (arrowhead) posterior to the front plate, anterior to the back plate, and extending from the 6-o’clock position to the 10-o’clock position prior to vitrectomy. B, Diagnostic B-scan ultrasonography exhibited an anterior vitreous band (arrow) and tractional retinal detachment due to epiretinal membrane from epithelial downgrowth (arrowheads) and choroidal detachment (asterisk). The tractional retinal detachment induced by the epiretinal membrane was most prominent anteriorly but extended across the posterior pole.

At his visit to us, visual acuity was 8/200 OD and 20/20 OS. No afferent pupillary defect was identified. Intraocu- A B lar pressure was soft to palpation OD and 14 mm Hg OS. Slitlamp examination revealed an intraprosthetic membrane (Figure 1A). B-scan ultrasonography revealed anterior vitreous bands, tractional retinal detachment (TRD), and a small choroidal detachment (Figure 1B). Review of B-scan ultrasonographic images performed 2 months pre- viously, before KPro placement, showed a normal posterior segment. A 23-gauge pars plana vitrectomy was performed to repair the TRD. Pars plana vitrectomy revealed a dense anterior vitreous band contiguous with a TRD and C D epiretinal membrane (ERM) extending across the macula. Extensive membrane peeling was performed, followed by fluid-air exchange, endolaser, and silicone oil injection. A large ERM specimen from the macula was sent for histopathologic evaluation. Microscopic evaluation of the ERM revealed mucosal epithelium containing goblet cells on hematoxylin-eosin, periodic acid–Schiff base, and Masson- Trichrome staining, consistent with ED (Figure 2). Im- munohistochemical analysis with cytokeratin showed positive staining, revealing epithelial cells lining one side Figure 2. Histopathologic photomicrographs. A, Histologic examination of the ERM (Figure 2). At the patient’s 2-month follow- demonstrates epithelial cells (arrowheads) within the fibrous tissue of the up, slitlamp examination revealed recurrent intrapros- epiretinal membrane (asterisk) displayed in a sheetlike configuration (hematoxylin-eosin, original magnification ϫ200). B, Foci of nonpigmented thetic membrane and flat retina by indirect ophthalmos- epithelium (arrowheads) are present within the fibrous tissue of the epiretinal copy and optical coherence tomography. membrane (asterisk) (periodic acid–Schiff, original magnification ϫ100). Inset, Goblet cell (arrowhead) with mucin at high magnification (periodic Comment. Epithelial downgrowth of the posterior seg- acid–Schiff, original magnification ϫ400). C, Noncollagenous epithelium stains red, sparing mucin-containing goblet cells (Masson trichrome, original ment is rare but can manifest within months after eye sur- magnification ϫ200). D, Cytokeratin stains positive for epiretinal membrane gery. McDonnell et al2 reported ED occurring 3 months af- (immunohistochemical stain [Dako Corp], original magnification ϫ200). ter ruptured globe repair, lensectomy, and pars plana vitrectomy, wherein TRD and ERM were found to consist ministration in 1992 and has demonstrated ED in only 2 of nonkeratinized, stratified squamous epithelium. Our case cases. Both cases had ED localized to the anterior cham- demonstrates a similar rapid progression of ED into the pos- ber due to full-thickness tissue melting at the KPro- terior segment after surgery. B-scan ultrasonography docu- cornea junction from ocular cicatricial pemphigoid.4 To our mented a normal-appearing posterior segment before KPro knowledge, there have been no published reports of ED placement. Two months after KPro placement, B-scan ul- after Boston KPro placement involving the posterior seg- trasonography showed the large TRD due to ED. ment. In our case, histologic review confirmed that ED of Epithelial downgrowth after KPro placement has been the posterior segment occurred after KPro placement. a subject of historical interest. Girard3 observed that ED Histopathologic findings of ED typically consist of non- only occurred in early KPro models previous to 1972. The keratinized, stratified squamous or conjunctival epithe- Boston KPro was approved by the US Food and Drug Ad- lium extending over the posterior cornea or anterior sur-

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©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/23/2021 face of the iris from an anterior wound site. In phakic or knowledge of uveal effusion and bilateral angle-closure pseudophakic eyes, the posterior lens capsule serves as glaucoma associated with bupropion use. a barrier preventing further advancement of the epithelium into deeper structures of the eye. Epithelial down- Report of a Case. A 40-year-old healthy white woman growth of the posterior segment can occur when this bar- with a history of depression had bilateral blurry vision rier has been disrupted (aphakia, lens luxation or starting the morning of her visit. Her ocular history was subluxation, iridodialysis) or bypassed (trauma, scleral significant only for myopia. She reported excellent vi- buckle intrusion).5 sion with −6.00–diopter sphere (DS) contact lenses prior Many treatments for ED have been described, includ- to her visit. Her only medications were ibuprofen, last ing cryotherapy, radiation, alcohol, steroids, antimetabo- used 1 month prior, and bupropion hydrochloride, 100 lites such as fluorouracil, and complex surgical proce- mg 3 times a day, which she started 2 weeks prior. Ten dures, each with varying rates of success and recurrence.6,7 years earlier, she had taken an uncertain dose of bupro- Although our case demonstrates successful surgical re- pion for an unknown duration without incident. pair of the TRD, the likelihood of ED disease progres- At her initial visit, visual acuity was 20/200 OD and sion remains high. Further study is needed to better un- 20/400 OS while wearing −6.00-DS contact lenses. In- derstand the etiology, diagnosis, and management of ED traocular pressure was 35 mm Hg OU, both pupils re- in this clinical setting. acted to light, and slitlamp examination revealed mild corneal edema and shallow anterior chambers bilater- Brett P. Bielory, MD ally (Figure 1A and B). Gonioscopy revealed apposi- David Jacobs, MD tional angle closure bilaterally (Figure 1C and D). Fun- Eduardo Alfonso, MD dus examination showed healthy nerves with a cup-disc Victor L. Perez, MD ratio of 0.2 OU. A diagnosis of bilateral angle-closure glau- Sander R. Dubovy, MD coma was made. Treatment was started in the emer- Audina Berrocal, MD gency room with 1 dose of each of the following: pilo- carpine hydrochloride, 1%, eye drops; timolol maleate, Author Affiliations: Bascom Palmer Eye Institute, Miller 2%/dorzolamide hydrochloride, 0.5%, eye drops; bri- School of Medicine, University of Miami (Drs Bielory, Ja- monidine tartrate, 0.15%, eye drops; latanoprost, 0.005%, cobs, Alfonso, Perez, Dubovy, and Berrocal) and Ocular eye drops; and oral acetazolamide, 500 mg. Pathology Laboratory, Florida Lions Eye Bank (Dr Du- The next day in the Glaucoma Service, intraocular bovy), Miami. pressure was 22 mm Hg OU. Ultrasound biomicroscopy Correspondence: Dr Berrocal, Bascom Palmer Eye In- showed bilateral choroidal effusions causing shallow stitute, Miller School of Medicine, University of Miami, angles (Figure 1E and F), and B-scan ultrasonography 900 NW 17th St, Miami, FL 33136 (aberrocal@med showed diffuse 360° of suprachoroidal hypoecho- .miami.edu). genicity consistent with uveal effusions (Figure 1G and Financial Disclosure: None reported. H). Autorefraction demonstrated a myopic shift to Additional Contributions: Candace Waithe-Boodoo, Ran- −16.00 DS OU, supporting a diagnosis of bilateral dall Hughes, Sarah Miller, CRA, and Alexander Rodriguez, angle-closure glaucoma with myopic shift secondary to CRA contributed to data and photograph collection. uveal effusions. Bupropion, acetazolamide, and pilocar- 1. Zerbe BL, Belin MW, Ciolino JB; Boston Type 1 Keratoprosthesis Study Group. pine were discontinued, and treatments with predniso- Results from the multicenter Boston Type 1 Keratoprosthesis Study. lone acetate and cyclopentolate hydrochloride eye Ophthalmology. 2006;113(10):1779.e1-1779.e7. 2. McDonnell JM, Liggett PE, McDonnell PJ. Traction retinal detachment due drops were started. to preretinal proliferation of surface epithelium. Retina. 1992;12(3):248-250. Two days later, her visual acuity improved to 20/70 3. Girard LJ. Keratoprosthesis. Cornea. 1983;2:207-224. OD and 20/100 OS with contact lenses, her intraocular 4. Dudenhoefer EJ, Nouri M, Gipson IK, et al. Histopathology of explanted col- lar button keratoprostheses: a clinicopathologic correlation. Cornea. 2003; pressures normalized, and her angles were open. All 22(5):424-428. treatments with eye drops were stopped. At 1 week, 5. Wolter JR. Unusual epithelial downgrowth complicating retinal surgery. Am J Ophthalmol. 1977;84(5):750. her examination findings normalized (Figure 2A-D) 6. Vargas LG, Vroman DT, Solomon KD, et al. Epithelial downgrowth after clear and repeat ultrasound biomicroscopy (Figure 2E and cornea phacoemulsification: report of two cases and review of the literature. F) and B-scan ultrasonography (Figure 2G and H) Ophthalmology. 2002;109(12):2331-2335. 7. Shaikh AA, Damji KF, Mintsioulis G, Gupta SK, Kertes PJ. Bilateral epithelial showed complete resolution of the uveal effusions. downgrowth managed in one eye with intraocular 5-fluorouracil. Arch One month later, her visual acuity was 20/20 OU Ophthalmol. 2002;120(10):1396-1398. while wearing −6.00-DS contact lenses. She started treatment with escitalopram oxalate for depression. Nine months later, her examination findings remained stable without effusions.

Bilateral Uveal Effusion and Angle-Closure Comment. Drug-induced uveal effusions with resultant Glaucoma Associated With Bupropion Use bilateral angle-closure glaucoma and myopic shift are un- common but have been reported with a variety of medi- upropion hydrochloride, an aminoketone anti- cations, most notably sulfa-based medications such as depressant, is a dopamine reuptake inhibitor with topiramate.2 The mechanism for drug-induced uveal ef- norepinephrine and nicotinic acetylcholine re- fusions is unclear. Some cases appear to be dose depen- B 1 ceptor antagonist actions. We report the first case to our dent as lower doses of the inciting medication may not

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